The system of the invention comprises a plastic fluidic device having at least one reaction chamber connected to pumping structures through capillary channels and external linear actuators. The device comprises two plastic substrates, a top substrate and a bottom substrate containing capillary channel(s), reaction chamber(s), and pump/valve chamber(s)—and a flexible intermediate interlayer between the top and bottom substrate which provides providing a sealing interface for the fluidic structures as well as valve and pump diaphragms. Passive check valve structures are formed in the three layer device by providing a means for a gas or liquid to flow from a channel in the lower substrate to a channel in the upper substrate by the bending of the interlayer diaphragm. Furthermore flow in the opposite direction is controlled by restricting the diaphragm bending motion with the lower substrate. Alternatively check valve structures can be constructed to allow flow from the top substrate to the bottom substrate by flipping the device structure. Pump structures are formed in the device by combining a pump chamber with two check valve structures operating in the same direction. A hole is also constructed in the lower substrate corresponding to the pump chamber. A linear actuator—external to the plastic fluidic device—can then be placed in the hole to bend the pump interlayer diaphragm and therefore provide pumping action to fluids within the device. Such pumping structures are inherently unidirectional.
In one embodiment the above system can be used to perform immunoassays by pumping various reagents from an inlet reservoir, through a reaction chamber containing a plurality of immobilized antibodies or antigens, and finally to an outlet port. In another embodiment the system can be used to perform assays for DNA analysis such as hybridization to DNA probes immobilized in the reaction chamber. In still another embodiment the device can be used to synthesize a series of oligonucleotides within the reaction chamber. While the system of the invention is well suited to perform solid-phase reactions within the reaction chamber and provide the means of distributing various reagents to and from the reaction chamber, it is not intended to be limited to performing solid-phase reactions only.
The system of the invention is also well suited for disposable diagnostic applications. The use of the system can reduce the consumables to only the plastic fluidic cartridge and eliminate any cross contamination issues of using fixed-tipped robotic pipettes common in high-throughput applications.
U.S. Pat. No. 7,241,421 describes a miniaturized analysis cartridge comprised of three layers, which incorporates uni-directional valves and uni-directional pumps. An injection molded layer of silicone rubber is inserted between two injection molded substrates. The silicone rubber layer serves several purposes. First, it serves as a flexible valve seat for the uni-directional valve. Second, it serves as a flexible pump membrane that is actuated by an external linear actuator. Third, it serves as a soft, compressible layer to seal the entire microfluidic network, including pumps, valves, microchannels, and reservoirs. The two injection molded substrates are compressed and heat staked in order to form a leak-free seal.
However, valves as described in U.S. Pat. No. 7,241,421 have a very limited working range due to the compression of the sealing process. A torque develops in the valve seat due to compression of the rubber, which causes the valve to open. Therefore, valves as described in U.S. Pat. No. 7,241,421 do not achieve a leak-free seal while performing consistently.
A need for a valve which closes instead of opens upon compression of the rubber due to the sealing process arose. Such an invention would render achievement of both an effective seal and an operational valve mutually inclusive over a reasonable process range and would enable consistent production of devices similar to U.S. Pat. No. 7,241,421. The present invention describes such a valve structure that allows for consistent valve operation over a compression range of 30-100 microns.